DESCRIPTION: State the application's broad, long-term objectives and specific aims, making referenceto the health relatedness erfthe project. Describe concisely the experimental design and method for achieving these goals. Avoid summaries of past accomplishments and the use of the first person. This abstract is meant to serve as a succinct and accurate description of the proposed work when separatedfrom the application. If the application is funded, this description as is, will become public information. Therefore, do not include proprietary/confidential information. DO NOT EXCEED THE SPACE PROVIDED. A major challenge to the medical sciences is understanding the mechanisms of, and development of treatments for, the large group of disorders that are primarily genetic in origin. The techniques of molecular biology have made it possible to identify and characterize defective genes and proteins, and to potentially treat disease by gene replacement therapy, but wide gaps in knowledge of the cellular and molecular mechanisms of pathogenesis remain. Because of their broad education in the biological medical sciences and their direct involvement in the health and productivity of animals, veterinarians are ideally suited to play major roles in research into the basic mechanism involved in genetic diseases, gene therapy, and in the identification and engineering of genes that will be important in producing disease resistant livestock. We have established an extensive research program aimed at understanding the molecular pathogenesis and treatment of genetic diseases by utilizing animal models of human genetic disease. Studies on individual animal models that can address important scientific questions concerning mechanisms and treatments are supported by a large number of NIH and private foundation grants to investigators in the Veterinary School and other biomedical entities on the campus. This continuation grant proposes to attract and train talented veterinary scientists in medical and molecular genetics research, emphasizing those fields which provide the greatest potential to advance the understanding, treatment, and prevention of diseases in which genes play a major role. We expect the program to produce a cadre of outstanding young scientists who will not only advance knowledge, but who will, through their influence on the profession and related fields, serve as leaders in the further development of medical genetics in veterinary medicine. With the recent excitement generated byi the human genome project and the first successes in human gene therapy trials, we expect an increasing number of veterinarians to be interested in obtaining advanced scientific training in genetics. Increasing the number of comparative medical scientists with solid training in molecular biology at this time will result in increased availability to the biomedical research community of animal models of human genetic diseases that are characterized in sufficient depth to allow studies that will advance general understanding of genetic diseases and their treatments. Our trainees are beginning to influence the field by their presence on the faculties of veterinary schools. PERFORMANCE SITE(S) (organixation, city, state) University of Pennsylvania Philadelphia, PA 19104 Children' s Hospital of Philadelphia Philadelphia, PA 19104 KEY PERSONNEL. See instructions on Page 11 .Use continuation pages as neededto provide the required information in the formal below. Name Organization Role on Project Wolfe, J.H. University of Pennsylvania Program Director See Table IE Training Faculty PHS 398 (Rev.5/95) Page _2 J J Number pages consecutively at the bottom throughout the application. Do not use suffixes such as 3a, 3b. __ ^[unreadable]~. Wolfe NN ^P Program Director (Last, first, middle):. Type the name of the program director at the top of each printed page and each continuation page. (For type specifications, see instructions on page 6.) INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARD (Substitute Page)